Trajectories of pain and depressive symptoms among people living with low back pain during the COVID-19 pandemic: a 24-month longitudinal study

During the first 2 years of the COVID-19 pandemic, subgroups of people experience deterioration/improvement in pain and depressive symptoms but that revert back to baseline.


Introduction
The coronavirus disease-2019 (COVID-19) pandemic and its health, social, and economic consequences initially led to a global impact on mental health compared with pre-COVID-19 levels. 37ockdowns and restrictions have affected people's lives, including limited social contact, increased global stress, decreased physical activity levels, and negative mental health effects. 3These effects could be amplified in vulnerable populations such as people with chronic low back pain (LBP). 3tudies investigating the worsening of pain severity during COVID-19 among people living with chronic pain were mainly cross-sectional and focused on perceptions of change in pain Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.symptoms. 38Other studies retrospectively reported pre-COVID-19 pain severity. 11,33These studies are limited by recall biases. 14,39,40oreover, a systematic review showed a rise in the prevalence and intensity of LBP related to COVID-19. 34nly a few longitudinal studies have considered pain characteristics among people with LBP during the pandemic.Studies comparing prepandemic and postpandemic scores point toward the presence of subgroups, with some individuals showing improved pain scores, whereas others showing pain deterioration. 1,10Similarly, unchanged pain, emotional distress, and opioid misuse patterns were found over a 1-year period among adults with chronic pain, 27 whereas improvements in pain intensity and depression scores were found in patients with chronic pain when studied over the course of the first 2 years of the pandemic. 47uch understanding of individuals' long-term pain and psychological distress trajectories taking into account prepandemic status, however, is lacking.It is possible that individual's stress response plays a role in the observed interindividual variability in pain trajectories. 9,31,43urprisingly, although the prevalence of psychological distress among general population during the COVID-19 pandemic has been well covered, biological variables such as cortisol have been less studied. 45Cortisol is a hormone produced by the adrenal glands in response to stress, and it plays a vital role in regulating various physiological processes. 46In general, high levels of cortisol have been associated with increased pain sensitivity and exacerbation of chronic pain conditions. 18Elevated cortisol levels in response to stress have also been associated with major depressive disorder. 29urther research, particularly when pre-COVID-19 data are available, is crucial to understand the longitudinal evolution of onset outbreak and post-COVID-19 pain-related outcomes as well as identifying subgroups of patients with LBP who share similar patterns.Well-designed studies incorporating trajectory analysis can help elucidate how the COVID-19 pandemic has influenced long-term pain outcomes among people living with LBP and their associated factors.The findings of such research can inform clinical practice, public health interventions, and strategies for managing LBP in the aftermath of the pandemic.Hence, this study aimed to (1) identify trajectories of pain intensity and depressive symptoms and (2) determine whether prepandemic and onset outbreak variables (including biological measurements of stress) are associated with trajectory groups.

Methodology
STROBE reporting guidelines were followed.

Recruitment and procedures
This cohort study was conducted using data from the Quebec LBP Study (QLBPS). 32This cohort began recruiting participants with LBP in 11/2018 (clinicaltrials.gov:NCT04791891) through mostly social and mass media, individual and institutions by email list servers, emails to patient organizations and professional societies, unions of workers at risk of LBP, and health care clinics.Participants completed online questionnaires over a 24-month period.In March 2020, 1 month after the declaration of the state of emergency in Quebec, Canada, all active QLBPS cohort participants were invited to participate in a special COVID-19 study, which required them to complete specific questionnaires every 3 months until July 2022 and, if interested, provide hair sample 3 months after the start of the pandemic (June 2020).For this study, eligible participants were adults ($18 years old) fluent in French, who had LBP for more than 3 months, were active participants in the QLBPS, and completed at least 2 time points of the COVID-19 study questionnaires.

Outcomes
Pain intensity was evaluated using the Numeric Rating Scale (NRS-11) from the Canadian Minimum Dataset for Chronic LBP Research, as follows: "In the past 7 days, how would you rate your average lower back pain?". 23Possible answers range from 0 (no pain) to 10 (worst imaginable pain).Depressive symptoms were evaluated using the Emotional Distress-Depression PROMIS Short-Form 4a, 21 which had 4 questions (In the past 7 days, (a) I felt hopeless, (b) I felt helpless, (c) I felt depressed, and (d) I felt hopeless) on a 5-point Likert scale (Cronbach alpha .0.90 19 ).The raw score was computed summing the 4 items and then rescaled into a T-score as per recommendations about this scale. 36

Potential predictors
The predictors of trajectory groups included pre-COVID-19 and onset outbreak COVID-19-related variables.
The pre-COVID-19 variables were taken from the latest evaluation (between 0 and 17 months) from the QLBPS (nearest to the COVID-19 study time 0), which was based on the Canadian Minimum Dataset for Chronic LBP Research. 2,13,23This included the following characteristics: LBP status and type; comorbid painful conditions; history of LBP surgical interventions; pain interference (PROMIS Short-Form 4a 36 ); LBP treatments (opioid use, infiltrations/injections, exercise therapy, and psychological counselling); LBP-related workplace absenteeism and compensation benefits; physical function (PROMIS Short-Form 4a 36 ); kinesiophobia (an item from the STarT Back Screening Tool 5 ); catastrophizing (an item from the STarT Back Screening Tool 5 ); LBP-related lawsuits and legal claims; substance abuse; sociodemographic profile (age, sex identity, indigenous membership, racialized groups membership, employment, and education level); cigarette use; and height/weight to calculate body mass index.Sex at birth and administrative region were also available in the QLBPS.Internal consistency for the multi-item measures of the PROMIS is excellent (Cronbach alpha .0.90 19 ).
Onset outbreak COVID-19 pandemic variables were selected by a group of pain researchers, clinicians, and persons with lived experience involved in the QLBPS who developed a questionnaire to measure stressors related to the onset of the pandemic.Acute stress disorder symptoms (19-item Acute Stress Disorder Scale) were collected by asking the extent to which they experienced symptoms of acute stress such as hypervigilance, numbing, arousal, and reactivity when they thought or heard about COVID-19 on a scale from 0 (not at all) to 4 (extremely) (Cronbach alpha .0.90). 8Participants also reported their level of stress by answering the following questions developed for the purpose of this study: "To what extent do you find the COVID-19 pandemic stressful?"and "To what extent do you find the lockdown measures associated with the COVID-19 pandemic stressful?"with possible answers ranging from 0 (not at all) to 10 (extremely). 33In addition, samples measuring 6 centimeters of hair were collected between June 2020 and July 2020 by mail to assess cortisol levels (stress hormone).Samples were taken by the participants themselves with instructions and material sent to them by mail.As hair grows an estimated 1 cm/month, the centimeters closest to the scalp represent the previous month. 17y collecting 6 cm of hair sample, it was possible to produce an estimate of cortisol levels on average in the first 3 months of the pandemic (first 3 cm of hair closest to the scalp-March 2020 to June 2020) and in the 3 months before the onset of the pandemic (next 3 cm of hair-December 2019 to March 2020) to obtain percentage of changes in cortisol levels.Hair samples provide a cumulative measure of cortisol levels, thus eliminating the drastic variations by timing of sample collection using saliva, urine, or serum. 24The hair samples were stored at room temperature in a dark and dry environment.The samples were centrally assayed to determine hair cortisol.Information regarding COVID-19 diagnosis during each evaluation was collected by inquiring, "Have you been diagnosed with COVID-19 (confirmed by a test that was administered by a health care professional)?" Finally, given that the pre-COVID-19 questionnaire was not filled at the same time by all participants (we took their latest QLPBS survey completed from this cohort before the pandemic), a time variable representing the number of months elapsed between the pre-COVID-19 QLPBS survey and the pandemic onset was calculated.

Statistical analysis
The pain intensity and depression scores collected from time 0 (April 2020) to time 9 (July 2022) were modelled into trajectories using group-based trajectory modelling (GBTM). 28Trajectory groups were then used as categorical dependent variables.
The GBTM determines the form and number of groups that best fit the data and provides a metric for evaluating the precision of group assignments. 30It tolerates missing data well. 30Up to 5 trajectories (groups) and 3 trajectory shapes (linear, quadratic, and cubic) were tested.To select the right number of trajectories, several censored normal (CNORM) models were evaluated.We evaluated up to 5 distinct trajectories and 3 trajectory shapes: (1) linear (straight line), (2) quadratic (U-shaped curve/parabola), and (3) cubic.Each trajectory within the same model could have its own shape.Therefore, there were 3 possible combinations of trajectory shapes for models including only 1 trajectory (eg, 1, 2, or 3), 9 models with 2 trajectories (eg, 11, 22, 33, 12, 13, 23, 21,  31, and 32), 27 models with 3 trajectories (eg, 112, 221, and 333), 81 models with 4 trajectories (eg, 1121, 3221, and 3333), and 243 models with 5 trajectories (eg, order: 11211, 32211, and 33333).In total, GBTM led to the testing of 363 models.For pain and depression, respectively, the models with the lower value (absolute value) of the Bayesian information criterion (BIC), with posterior probabilities .0.70, and with all trajectories being represented by at least 5% of participants were selected. 28The trajectory group profiles were compared using medians and percentages and the 95% confidence interval for multinomial proportions and medians.
Multiple logistic regression models using LASSO with k-fold cross-validation (k 5 10) were then applied across the study sample to assess the association between prepandemic and onset outbreak variables (independent variables) and dichotomized pain intensity trajectory groups (dependent variables) while accounting for covariables.In the 4 regression models, pain intensity trajectory groups were dichotomized as follows: (1) stable severe and moderate pain intensity vs other trajectory groups, (2) U-shape pain intensity vs other trajectory groups, (3) inverted U-shape pain intensity vs other trajectory groups, and (4) stable mild pain intensity vs other trajectory groups.As for depressive symptoms trajectory groups, 3 regression models were compared: (1) severe slightly improving and stable moderate depressive symptoms vs other trajectory groups, (2) stable mild depressive symptoms vs other trajectory groups, and (3) stable none and very mild depressive symptoms vs other trajectory groups.Although a broad set of a priori determined variables potentially associated with changes in pain intensity and depressive symptoms were included in the bivariate logistic regression models, only the most valuable variables according to the Least Absolute Shrinkage and Selection Operator (LASSO 41 ) regression were included in the final model.Age, sex, acute stress disorder symptoms, how stressful the COVID-19 pandemic was perceived, how stressful the lockdown measures associated with the COVID-19 pandemic were perceived, and having received a COVID-19 positive screening were forced in the models.Multicollinearity was tested according to variance inflation factors. 44inally, the comparison of the pre-onset of the COVID-19 pandemic and post-onset of the COVID-19 pandemic percentage of changes in cortisol levels (pg/mg) among the trajectory groups was conducted using medians and their corresponding 95% confidence intervals in a subset of participants.Multiple logistic regression models, which included the pre-onset of the COVID-19 pandemic and post-onset of the COVID-19 pandemic percentage changes in cortisol levels, were adjusted for various factors.These factors encompassed age in years, pre-onset of the COVID-19 pandemic pain intensity, pre-onset of the COVID-19 pandemic depressive symptoms, pre-onset of the COVID-19 pandemic pain interference, pre-onset of the COVID-19 pandemic physical function, scores indicating the perception of the COVID-19 pandemic as stressful, and the perception of lockdown measures associated with the COVID-19 pandemic as stressful during the early pandemic stages, as well as the duration in months between the pre-onset of the COVID-19 pandemic and onset-of-pandemic surveys.All analyses were performed using SAS (version 9.4, Cary, NC).

Results
The analysis was conducted among 291 participants living with LBP for at least 3 months (Fig. 1).Percentage of missing data ranged from 0.7% at baseline to 55% at 24-month follow-up, with an average of 36% of missing data per time point.The sample characteristics are shown in Table 1.Mean age at the onset of pandemic was 47.4 6 12.3 years, and 69.4% were female.
The best fit for the data keeping at least 5% of participants in the smallest group trajectory was a five-trajectory model for pain (23321) and a five-trajectory model for depressive symptoms (11111).Model fit indices for the best 15 models tested are shown in Appendix A and B, http://links.lww.com/PR9/A234.Descriptively, the stable mild pain intensity trajectory was characterized by the absence of participants working or current smokers, a low percentage of widespread pain and catastrophic thinking, and low average pain intensity before COVID-19.The severe pain trajectory was characterized by a high percentage of people reporting widespread pain and catastrophizing thinking, as well as high average pain intensity, depressive symptoms, and high levels of pain interference before COVID-19 (Table 2), and a low percentage of people reporting pain less than half the days in the past 6 months.In the multivariate logistic regression (Table 3), the stable severe and stable moderate pain intensity trajectories were associated with having pain every day or nearly every day in the past 6 months (OR 5 3.3; 95% CI 5 1.4, 7.7), widespread pain (OR 5 2.7; 95% CI 5 4.0, 5.2), and higher pain intensity before COVID-19 (OR 5 1.5; 95% CI 5 1.3, 1.9) compared with the other 3 trajectories.The U-shape trajectory was associated with less pain interference before COVID-19 (OR 5 0.9; 95% CI 5 0.8, 0.98) and having COVID-19 at any point (OR 5 3.9; 95% CI 5 1.3, 11.3) compared with the other 4 trajectories.The inverted U-shape was associated with lower pain intensity before COVID-19 (OR 5 0.8; 95% CI 5 0.7, 0.9) compared with the other 4 trajectories.The stable slight pain trajectory was associated with pain that radiates down the leg (OR 5 0.1; 95% CI 5 0.1, 0.7) and widespread pain (OR 5 0.1; 95% CI 5 0.01, 0.6) compared with the other 4 trajectories.With the exception of having COVID-19 at any point, none of the factors associated with the pandemic were associated with trajectory groups.
Descriptively, the trajectory of severe depressive symptoms was characterized by a high percentage of people reporting widespread pain and participants treated with opioids.Likewise, this trajectory showed a high score of depressive score before COVID-19, high levels of acute stress disorder symptoms, high levels of stress related to the pandemic and to the lockdown measures, and lower levels of physical function before COVID-19 (Table 4).In the multivariate analysis (Table 5), each additional increase of 1 point in depressive symptom score before COVID-19 (OR 5 1.2; 95% CI 5 1.1, 1.2), acute stress disorder (OR 5 1.1; 95% CI 5 1.03, 1.1), and finding lockdown measures associated with the COVID-19 pandemic stressful (OR 5 1.3; 95% CI 5 1.04, 1.6) were associated with an increase in the odds of having severe depressive symptoms compared with the other 3 trajectories.
Of the 291 participants, 105 agreed to provide a hair sample (other participants either could not be reached by phone to explain this procedure, refused, or did not have hair long enough).Among these 105 individuals, after excluding 3 outliers (with cortisol values $ 3 SDs), 74 provided a sufficient hair length (6 cm).
Although the confidence intervals do not indicate a significant difference between the trajectory groups of pain intensity (Fig. 4) and depressive symptoms (Fig. 5), there was an increasing trend in cortisol levels in the post-onset of the COVID-19 pandemic measurements for the stable mild and inverted U-shape pain intensity groups, as well as for the stable none and stable mild trajectories of depressive symptoms.In the binary multiple logistic regression models that include the pre-onset of the COVID-19 pandemic to post-onset of the COVID-19 pandemic percentage of change in cortisol levels and subjective stress measures, the pre-onset of the COVID-19 pandemic to post-onset of the COVID-19 pandemic percentage of change in cortisol is not significantly associated with any trajectory of pain or depressive symptoms (Table 6).

Discussion
We investigated trajectories of pain intensity and depressive symptoms beyond the early stages of the COVID-19 pandemic in a cohort of participants living with chronic LBP.We found 5 distinct trajectories of pain intensity and 4 distinct trajectories of depressive symptoms, respectively.Pre-COVID-19 pain characteristics were associated with pain intensity trajectory groups,  whereas acute stress reactions were associated with depressive symptom trajectory groups.Objective stress measure (cortisol) was not predictive of either group trajectory.
Overall, more than two-thirds of individuals experienced stable pain intensity over a two-year period, regardless of challenges or opportunities provided by the COVID-19 pandemic.This is consistent with other trajectory analyses of individuals living with LBP conducted in prepandemic states showing that ,15% of cohort participants show fluctuations in pain states. 20It is also consistent with another study after individuals with chronic pain seeking tertiary care during the pandemic. 47Variability in pain states tends to be identified in studies with shorter time between measurements (eg, weekly). 20t is important to note, however, that subgroups of participants experienced temporary deterioration (22.7%) or improvement (8.3%) over the first months of the pandemic, which then reverted back to baseline levels.This could be associated with disruptions in daily routines and access to care.A recent study showed that for   22 For others, access to virtual care was improved. 4Contracting COVID-19 in people with pre-existing chronic pain was associated with a U-shape trajectory in our study, but did not differentiate between the other trajectories.Little available data exist on this topic; it seems, however, that COVID-19 infections are not always associated with worsened pain states; rather, biopsychosocial factors are more strongly associated with changes in pain states during the pandemic. 38ore severe pain intensity trajectories were associated with pain frequency, widespread pain, and higher pain intensity before COVID-19.Our findings suggest that individuals with higher pain intensity levels before the pandemic were more likely to continue experiencing significant pain throughout the pandemic.Our results also suggest that individuals with pain extending beyond the low back region may be at a higher risk of experiencing more severe and persistent pain during the pandemic.Widespread pain is often associated with conditions such as fibromyalgia, which can contribute to increased pain sensitivity and a higher likelihood of chronic pain. 26lthough between March 2020 and June 2022, there were 6 waves of COVID-19 cases, 15 with their respective response strategies such as mobility restrictions, confinement, and vaccination, 12,16,42 we found long-term stable depression symptoms in 4 of 5 trajectory groups during this period.This supports the idea that the local outbreak of the pandemic did not have a serious negative impact on depressive symptoms among people with LBP.It could be that our participants did not perceive the major changes of daily life during the pandemic and therefore showed stable trajectories over the course of this period.Also, it is possible that people with pre-existing mental health conditions may have had established treatment plans or support systems in place before the pandemic.This previous care could have helped them maintain stability or prevent worsening of their depression symptoms.The only previous 2year study in people with chronic pain revealed improvements in pain intensity and depressive scores. 47Those finding supports evidence of resilience among patients receiving treatment for chronic conditions during the COVID-19 pandemic.However, that study did not evaluate trajectories of pain intensity or depressive symptoms.
In our study, the multivariate analysis revealed that higher scores of pre-COVID-19 depressive symptoms, acute stress disorder, and finding COVID-19 lockdown measures stressful were associated with stable moderate and severe slightly improving trajectories of depressive symptoms.These results are in line with a populationbased study from Switzerland following people between July 2020 and December 2021, in which the highly affected trajectory of depressive symptoms had a greater proportion of individuals with higher levels of past depression, 35 and acute stress disorder is a psychological state that can occur after experiencing a traumatic event, such as a life-threatening situation. 7The symptoms of acute stress disorder include intrusive thoughts or memories of the event, avoidance of reminders of the event, negative mood, heightened anxiety, and increased arousal.If left untreated, acute stress disorder can potentially lead to the development of post-traumatic stress disorder or other mental health conditions, including depression. 6he COVID-19 pandemic has brought about a range of stressors that can trigger or exacerbate mental health issues.Lockdown measures, such as social isolation, quarantine, financial uncertainties, disruptions to daily routines, and fear of contracting the virus, have had a profound impact on people's lives.These stressors can lead to feelings of helplessness, loneliness, anxiety, and depression.Experiencing acute stress disorder in response to highly stressful events associated with the pandemic, along with finding the lockdown measures stressful, can contribute to the development of severe and persistent depressive symptoms.The combination of acute stress, ongoing stressors, and social isolation can create a challenging environment for mental well-being and increase the risk of developing or worsening depressive symptoms.For this reason, engaging in self-care practices, maintaining social connections through virtual means, and seeking support from loved ones could be beneficial in coping with the challenges of the pandemic.It is essential to continue monitoring and addressing the physical and mental well-being of individuals with low back pain, as well as providing appropriate support and interventions to manage their symptoms effectively.
The finding of a nonstatistically significant, but slight increasing trend in cortisol levels post-onset of the COVID-19 pandemic compared with pre-onset of the COVID-19 pandemic levels in all groups suggests that the experience of the pandemic may have triggered a stress response within the study population.The small sample size and lack of statistical power are, however, limiting our capacity of interpretation.Still, the COVID-19 pandemic has brought about various stressors, including fears about health, economic uncertainties, social isolation, and disruptions to daily routines.These stressors can activate the body's stress response system, leading to increased cortisol production.It is important to note that a slight increasing trend in cortisol levels does not necessarily indicate pathological or clinically significant changes.It most likely reflects an adaptive physiological response to a stressful event.However, prolonged or chronically elevated cortisol levels can have negative physical and mental health consequences, including impaired immune function, increased risk of mental health disorders, and other physiological disturbances. 25

Strengths and limitations
Strengths of this study include the longitudinal design with a longterm follow-up and the availability of prepandemic data.This is crucial to examine the mental health effects of the COVID-19 pandemic.However, there was a small sample size to evaluate pre-post COVID-19 differences of cortisol levels.In addition, it is important to note that our study is specific to individuals with LBP living in Quebec and may not generalize to other populations or individuals with different types of pain conditions.Nonetheless, the online recruitment allowed to recruit a diversified sample of persons living in all Quebec regions, and the QLBPS participants were found to be representative of other large random samples of adults living with chronic LBP in Canada and elsewhere in terms of proportion of women, education level, smoking, and pain intensity. 2

Figure 1 .
Figure 1.Flowchart of the study.

Figure 4 .
Figure 4. Cortisol levels by trajectories of pain intensity.Median and 95% confidence interval.

Figure 5 .
Figure 5. Cortisol levels by trajectories of depression.Median and 95% confidence interval.

Table 1
Sample characteristics.

Table 2
Sample characteristics by trajectories of pain intensity.

Table 2 (
continued)Sample characteristics by trajectories of pain intensity.

Table 3
Multivariable binary logistic regression models used to identify participants' sociodemographic and clinical characteristics associated with trajectories of pain intensity (n 5 230).
Significant associations were bolded.In the model of severe or stable moderate pain intensity trajectories, we forced age, sex, and finding the COVID-19 pandemic stressful and having COVID-19 at any point.In the model of Ushape pain intensity trajectories, we forced age, sex, acute stress disorder, finding the COVID-19 pandemic stressful, finding lockdown measures associated with the COVID-19 pandemic stressful, and having COVID-19 at any point.In the inverted U-shape pain intensity trajectory, and the slight pain intensity trajectory models, we forced age, sex, acute stress disorder, finding the COVID-19 pandemic stressful, finding lockdown measures associated with the COVID-19 pandemic stressful, and having COVID-19 at any point.

Table 4
Sample characteristics by trajectories of depressive symptoms.
states remained overall relatively stable for a majority of individuals, pointing to a relative resilience in this population.Results also indicate that for some, early adjustments to the pandemic negatively impacted physical and mental health status; these findings combined suggest the need to deploy targeted prevention and acute intervention strategies during major events (eg, pandemic and natural disasters) for more vulnerable individuals.Those might be individuals with higher levels of pain interference or lower levels of physical functioning.DisclosuresM.G.P. received honoraria from Canopy Growth and research funds from Pfizer ULC Canada for work unrelated to this study.Coauthors do not have conflicts of interest to declare.

Table 6
Subgroup analysis.Association between cortisol and pain intensity trajectories and depressive symptoms adjusted for several variables.* Stable mild pain (n 5 5) vs other trajectories (n 5 62) were not included because of small sample size.